Genetics of Postpartum Depression in Affective Disorders

描述（由申请人提供）：这个职业发展奖的建议是一个五年计划，将使候选人发展成为一个独立的研究人员在情感障碍的遗传学，重点是女性的精神触发症状。该候选人是一名接受过情绪障碍培训的学术精神病学家，目前正在寻求遗传学和遗传流行病学方面的进一步培训。J. Raymond DePaulo博士是情感障碍遗传学研究小组的主任和约翰霍普金斯精神病学系的主席，他将指导候选人对精神病患者进行遗传研究。约翰霍普金斯公共卫生学院教授特里·贝蒂博士将指导候选人使用统计方法和遗传流行病学。北卡罗来纳州大学精神病学教授兼主席大卫·鲁宾诺博士和生殖内分泌学研究单位主任彼得施密特博士将指导候选人性腺类固醇的神经行为影响以及女性心理健康的临床和表型问题。该培训计划将通过一项研究计划来加强，该研究计划基于以下假设：患有产后抑郁症的女性对正常激素变化的时间具有遗传脆弱性，该正常激素变化包括对雌激素敏感的基因（或基因）的变异。这项研究计划将利用以前收集的双相情感障碍和复发性重性抑郁症的家庭样本。根据初步的数据，证明产后抑郁发作的家庭与重性抑郁症和双相情感障碍，候选人将完成以下三个具体目标：1）完成连锁分析这一特点; 2）进行关联研究，专门检查含有雌激素的感兴趣区域中的基因，反应元素，因此可能易受产后期间发生的激素波动的影响;和3）开始收集患有重度抑郁症的妇女的试验性样本，包括有和没有产后抑郁症。拟议的研究是重要的，因为它将导致更好地了解产后抑郁症的病理生理学在情绪障碍的妇女，以及潜在的有助于了解在妇女作为一个群体中观察到的抑郁发作率增加。

DESCRIPTION (provided by applicant): This career development award proposal is a five-year plan that will enable the candidate to develop into an independent investigator in the genetics of affective disorders with an emphasis on hormonally-triggered symptoms in women. The candidate is an academic psychiatrist with training in mood disorders who now seeks further training in genetics and genetic epidemiology. Dr. J. Raymond DePaulo, Jr, director of the Affective Disorders Genetics Research Group and Chair of the Johns Hopkins Department of Psychiatry will mentor the candidate on conducting genetic research in the psychiatric patient. Dr. Terri Beaty, Professor at the Johns Hopkins School of Public Health, will mentor the candidate on using statistical methods and genetic epidemiology. Dr. David Rubinow, Professor and Chair of Psychiatry at the University of North Carolina and Dr. Peter Schmidt, Chief of the Unit on Reproductive Endocrinology Studies, will mentor the candidate in both the neurobehavioral effects of gonaldal steroids as well as clinical and phenotypic issues in women's mental health. The training program will be enhanced by a research plan based on the hypothesis that women with postpartum depressive episodes have a genetic vulnerability to times of normal hormonal change that consists of variation in a gene (or genes) that is estrogen responsive. The research plan will take advantage of previously collected family samples of bipolar disorder and recurrent major depression. Based on preliminary data demonstrating the familiality of postpartum depressive episodes in families with major depression and bipolar disorder, the candidate will complete the following three specific aims: 1) complete a linkage analysis for this trait; 2) perform association studies, specifically examining genes in regions of interest which contain estrogen-response elements and thus may be susceptible to the hormone fluctuations that occur during the postpartum period; and 3) begin collection of a pilot sample of women with major depression with and without postpartum depression. The proposed research is significant because it will lead to a better understanding of the pathophysiology of postpartum depression in women with mood disorders as well as potentially contribute to understanding the increased rate of depressive episodes observed in women as a group.